Sulfuric Acid → (E)-8-chloro-2,3,4,5-tetrahydro-2-methyl-5-(2-(pyridin-4-yl)prop-1-enyl)-1H-pyrido[4,3-b]indole
Reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][C:12]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)(O)[CH3:13])[C:6]3[CH2:21][CH2:22][N:23]([CH3:25])[CH2:24][C:5]=3[C:4]=2[CH:3]=1.S(=O)(=O)(O)O.[OH-].[K+]>>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:11]=[C:12](/[C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)\[CH3:13])[C:6]3[CH2:21][CH2:22][N:23]([CH3:25])[CH2:24][C:5]=3[C:4]=2[CH:3]=1Participants
Procedure
1-(8-Chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-2-(pyridin-4-yl)propan-2-ol (1 g, 2.81 mmol, 1 equiv.) was refluxed with 25% sulfuric acid (7 mL) for 2 h. The reaction mixture was cooled to 5° C. in ice-water bath. KOH (15% aqueous solution) was added dropwise to the reaction mixture until pH 9-10 was achieved. The reaction mixture was extracted with EtOAc (3×10 mL). The combined organic layer was washed with water (10 mL) followed by brine, dried over sodium sulfate and evaporated under vacuum. The crude product was purified by silica gel chromatography (100-200 mesh) using a gradient of MeOH-EtOAc (0-10%) followed by HPLC to provide pure product. 1H NMR (DMSO, Oxalate Salt) δ (ppm): 8.60 (d,2H), 7.62 (m,3H), 7.40 (s,1H), 7.30 (d,1H), 7.20 (d,1H), 4.40 (m,2H), 3.10 (m,4H), 2.99 (s,3H), 1.90 (s,3H).
Workup
- extractionThe reaction mixture was extracted with EtOAc (3×10 mL)
- washThe combined organic layer was washed with water (10 mL)
- dry with materialdried over sodium sulfate
- customevaporated under vacuum
- customThe crude product was purified by silica gel chromatography (100-200 mesh)
- customto provide pure product
Sources & evidence
- ORD record
- ord-b80d6dcda6964fcfa7745c75b2b9c385
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08906925B2
Reaction notes
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